OrganicAnion/Cation Transporters: From MolecularInsights to Clinical Impact and Nanotechnology Innovation

Abstract Organic anion and cation transporters (OATs and OCTs), members of the solute carriers (SLC)22 family, are critically involved in the transport of endogenous metabolites and xenobiotics across key barriers in the kidney, liver, and choroid plexus. While their role in small-molecule drug pharmacokinetics, drug–drug interactions, and clinical issues is well established, their potential interaction with nanomaterials remains a largely unexplored frontier. This is particularly significant given that the long-term retention of nanomaterials in vivo poses a major challenge to their clinical translation. We hypothesize that OATs and OCTs recognize specific nanomaterials as substrates, thereby mediating a novel and active elimination pathway that transcends conventional size-dependent filtration. This review systematically delineates the structural and functional basis of major OAT/OCT subtypes (e.g., OAT1–3, URAT1, OCT1–3) to establish a conceptual framework and then integrates this with current clinical applications and a brief discussion on the primary biological elimination routes of nanomaterials. By bridging these fields, this review aims to prompt a paradigm shift in nanomedicine design, advocating for the rational engineering of nanomaterial properties (e.g., size, charge, surface, shape) to engage with these transport systems. Ultimately, leveraging OAT/OCT pathways may unlock novel strategies to precisely control nanomedicine distribution and enhance clearance, thereby accelerating safe and effective clinical translation.